We have generated constructs for dbl expression by taking advantage of the availability of expression vectors carrying various cell type-specific transcriptional control elements. These constructs were used to generate several lines of transgenic mice carrying the = oncogene. Independent of the promoter used, transgenic mice exhibited a dominant bilateral dysplasia of the lens similar to that induced in transgenic mice by expression of the An genomic clone. We have identified a region of significant similarity shared among the predicted translational products of the human dbl proto-oncogene, the Saccharomyces cerevisiae cell division control gene, CDC24, and the human breakpoint cluster gene, bcr. Deletion of amino acid stretches of various lengths as well as conservative or radical substitutions within this region of similarity led to drastic reduction of the transforming activity of the dbl gene. We have used a highly transmissible retrovirus bearing dbl coding sequences to infect a variety of cell types in culture. A rat pheochromocytoma cell line, PC12, infected with this virus showed drastic alterations in morphology and loss of ability to differentiate into neuron-like cells in response to various stimuli.